PROJECT SUMMARY AND ABSTRACT It is estimated that Alzheimer's and other neurodegenerative diseases causing dementia will surpass cancer as the leading cause of death by the year 2040. Alzheimer's is the leading cause of dementia, followed by synucleinopathies, including dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD), Fronto-temporal dementia and Vascular dementia. Among clinical researchers focused on investigating the varying etiologies, genetic associations, biomarkers, and treatment options for Alzheimer's disease, there is an urgent need for effective tools to aid in the classification of dementia subtypes, in the earliest detectable stages of the pathophysiological process. To address this unmet need Advanced Brain Monitoring (ABM) proposes to leverage day and night assessment technologies to create an Integrated Neurocognitive and Sleep-Behavior Profiler for the Endophenotypic Classification of Dementia Subtypes (INSPECDS) to profile Alzheimer's and other dementias. The core components of the INSPECDS platform will be the Alertness and Memory Profiler (AMP), the Sleep Profiler, and integrated machine-learning, classification algorithms, hosted on a secure, cloud-based, infrastructure for automated data processing, analysis, and reporting. The AMP was developed and validated intially for the purpose of detecting the neurocognitive effects of sleep deprivation in adults diagnosed with obstructive sleep apnea but has more recently been applied to assess Alzheimer's and Parkinson's disease. The AMP is unique among neurocognitive testing platforms in that it is the only one which integrates advanced, electrophysiological measures (e.g., 24-channel, wireless EEG and ECG) during the performance of computerized neurocognitive tasks and has proven effective in characterizing cognitive decline in Alzheimer's. This advanced capability permits researchers to explore real- time relations between fluctuations in alertness, discrete cognitive functions, and specific neural processes believed to subserve observed performance deficits in Alzheimer's and other dementias. The Sleep Profiler is an FDA-cleared, easily applied, wireless-EEG device that was developed and validated to measure sleep architecture for in-home sleep studies with submental (chin) EMG and wireless accelerometers to monitor head and limb movements to quantify the characteristics of REM-sleep behavior disorder (RBD), considered to be a prodromal expression of synucleinopathy. Furthermore, the application of sophisticated, machine- learning, classification algorithms will streamline the processing and analyses of these data to derive statistical probabilities of Alzheimer's and other dementia subtypes. The overarching goal of the current, Direct-to-Phase II, SBIR project is to finalize implementation of a secure, cloud-based infrastructure to compile the data obtained from the AMP and Sleep Profiler, train classification algorithms to discriminate among Alzheimer's and other dementia subtypes, validate diagnostic accuracy, and integrate optimized classifiers within the cloud- based architecture. Once completed, the INSPECDS system will be the first clinical research tool of its kind and find immediate application in both university-based research settings and pharmaceutical industry clinical trials to aid in the endophenotypic stratification of Alzheimer's and other dementias.